Male Breast Cancer: An Understudied Malignancy

A Conversation With Sharon Giordano, MD, MPH, FASCO

Male breast cancer is a rare and understudied malignancy when compared with female breast cancer, with conflicting literature on survival outcomes in men and women. The ASCO Post spoke recently with breast cancer expert Sharon Giordano, MD, MPH, FASCO, Professor at The University of Texas MD Anderson Cancer Center, Houston. Dr. Giordano is part of the International Male Breast Cancer Program, which is an ongoing worldwide effort to shed light on this disease and guide better treatment and prevention strategies.

Participation in Clinical Trials

Why are men routinely excluded from breast cancer clinical trials?

Historically, men have been excluded from breast cancer clinical trials, but over the past decade or so, I think there has been a real effort to be more inclusive when writing criteria for clinical trials in breast cancer. Honestly, much of the exclusion was more or less accidental, as most people simply associate breast cancer as a female disease, so that’s how it was written into the trial accrual data.

That said, there are also some studies in which biologic differences led to men being excluded; for example, studies may look at hormonal therapy in which men might respond differently to treatment because of underlying variations in hormone levels. So, there are biologic differences that affect eligibility accrual criteria in certain trials.

Genetic Factors

Do we have a body of knowledge about the genetic factors that confer greater risk of breast cancer in certain men?

The most prevalent genetic factors in male breast cancer are the BRCA1 and BRCA2 mutations, and the BRCA2 mutation confers the highest risk for men. Typically, when I see male patients in my clinic, I recommend they meet with a genetic counselor to consider genetic testing.

Several other genes that might elevate the risk of breast cancer in men as well as in women have also been identified. Studies have looked at radiation exposure and elevated levels of estrogen, which might predispose men to breast cancer. However, the majority of men do not have any underlying genetic predisposition that we can identify. Currently, the evidence linking genetic or other biologic factors to the development of male breast cancer is inconsistent, and the disease appears to strike sporadically.

Racial Differences

Black men appear to be at greater risk of breast cancer than white men. Do we know why?

The short answer is no. The Surveillance, Epidemiology, and End Results data show a higher incidence rate among African American men than their white counterparts. Although I haven’t seen any data that drill into the high incidence rate among African American men, there certainly could be risk factors. For example, we know that obesity elevates the risk of breast cancer, and there is a higher level of obesity among African American men than non-Hispanic white men. However, this still remains speculative at this point.

Management Approaches

Although male and female breast cancers share similarities, are there different management approaches?

Studies looking at men with breast cancer show that generally, they have lower unadjusted rates of overall survival than do women with breast cancer. As for differences in treatment, since there are no randomized trials of local therapy that have focused on men, management approaches are deduced from studies on women with breast cancer. Most women with newly diagnosed breast cancer undergo lumpectomy and whole-breast irradiation, whereas men usually have a mastectomy with axillary lymph node dissection. Although uncommon in men, breast-conserving therapy is associated with about the same benefits as mastectomy, which suggests that data from trials of surgery in women may apply to men as well.

To me, the biggest difference in the treatment of male breast cancer centers on endocrine management. The tumors in men are more likely to be estrogen receptor–positive than in women. And we have less information about which estrogen-blocking therapies will work in men. The data we do have suggest that tamoxifen is similarly effective in men as in women. Moreover, older studies have shown that men with metastatic breast cancer treated with tamoxifen reaped clearly drawn benefits.

Perhaps a more difficult question centers on aromatase inhibitors. When they first came out, there was speculation that they would be fantastic for male patients because a lot of the estrogen is produced from conversion from androgens to estrogens. Although these drugs might be effective, the data so far indicate they don’t suppress estrogen in men nearly as well as in women.

Gynecomastia

Is gynecomastia in men a risk factor for breast cancer?

It probably is, but we don’t have data to prove it with certainty. The studies that have looked at it have been relatively small. It is not easy to tease out because gynecomastia is common in older men, and when you have such a common condition, it makes it difficult to know whether it’s an underlying risk factor. That said, most experts probably agree that it is a risk factor.

“Most important is to enroll more men with
breast cancer into clinical trials.”

— Sharon Giordano, MD, MPH, FASCO

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Male Breast Cancer Study

Given the paucity of men enrolled in breast cancer clinical trials, how are we increasing our knowledge about this disease?

It’s difficult without the data from clinical trials. First, I’ve been part of the International Male Breast Cancer Program, which is a consortium of investigators around the world who are interested in male breast cancer research. We collected tissue specimens from international institutions from about 1,800 men diagnosed with breast cancer over the past 20 years. And from these specimens, we did biologic studies to determine the differences between male and female breast cancers.

Second, we looked at whether we had enough men to do a treatment study. In the past, these attempts have failed simply because there are not enough patients. We opened the study for 18 months across all the centers, hoping to accrue 200 male patients, and we actually got over 500. The next step is to launch treatment clinical trials looking to answer questions such as the optimal endocrine therapy for a male patient.

Closing Thoughts

Could you share a few final thoughts?

Most important is to enroll more men with breast cancer into clinical trials. Right now, we’re extrapolating most of our treatment recommendations from trials that exclusively include women. Although breast cancers in men and women have similar characteristics, breast cancer in men has distinct features. To that end, we need to have a better understanding of the biology of male breast cancer to prevent its undertreatment. ■